Dynamic Sars-Cov-2-Specific Immunity In Critically Ill Patients With Hypertension

FRONTIERS IN IMMUNOLOGY(2020)

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摘要
BackgroundThe current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an unprecedented health crisis. The most common chronic illness among patients infected with SARS-CoV-2 is hypertension. Immune dysregulation plays an important role in SARS-CoV-2 infection and in the development of hypertension; however, the dynamic immunological characteristics of COVID-19 patients with hypertension remain largely unclear.MethodsIn total, 258 hypertensive patients infected with SARS-CoV-2 were included in this study. CD38(+)HLA-DR+ and CD38(+)PD-1(+) CD8(+) T cells, IFN gamma(+)CD4(+) and IFN gamma(+)CD8(+) T cells, the titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and SARS-CoV-2 throat viral loads were measured weekly over 4 weeks after the onset of symptoms. Clinical outcomes were also monitored.FindingsCD4(+) T lymphopenia was observed in 100% of the severe and critical cases. Compared with the surviving patients, the patients with fatal outcomes exhibited high and prolonged expression of CD38(+)HLA-DR+ and CD38(+)PD-1(+) on CD8(+) T cells, low expression of SARS-CoV-2-specific IFN gamma(+)CD4(+) and IFN gamma(+)CD8(+) T cells, low titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and high SARS-CoV-2 viral load during the illness. In the surviving patients, the viral load was significantly inversely correlated with SARS-CoV-2-specific IFN gamma(+)CD8(+)and IFN gamma(+)CD4(+) T cells, IgG, IgM, and IgA.InterpretationT lymphopenia is common in critical or severe COVID-19 cases with hypertension. Prolonged activation and exhaustion of CD8(+) T cells were associated with severe disease. The delayed SARS-CoV-2-specific antibody responses may be insufficient for overcoming severe SARS-CoV-2 infection in the absence of SARS-CoV-2-specific cellular responses.
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关键词
COVID-19, SARS-CoV-2, hypertension, T cell, CD4, CD8
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